Undifferentiated Carcinomas of the Pancreas Are Characterized by KRAS Mutant Allele-Specific Imbalance
Alyssa Krasinskas, A James Moser, Sheri Kavala, Simon Chiosea. University of Pittsburgh Medical Center, Pittsburgh
Background: Activating point mutations in codon 12 of the KRAS oncogene are present in the majority of pancreatic ductal adenocarcinomas (PDAs) and in pancreatic undifferentiated carcinomas with pleomorphic or osteoclast-like giant cells. The role of KRAS mutant allele specific imbalance (MASI), which is associated with increased mutant allele transcription and kinase activity, has not been systematically studied in carcinomas of the pancreas.
Design: KRAS mutational analysis was performed using direct Sanger sequencing. Peak heights of KRAS mutant and wild-type alleles were compared on sequencing electropherograms. KRAS MASI was defined in mutated cases as mutant allele peak (M) higher than or equal to the wild type (W) allele peak (M≥W). KRAS amplification (KRAS/CEP12 >2) was evaluated in a subset of cases (18 PDA, 9 undifferentiated carcinomas) using fluorescence in situ hybridization.
Results: KRAS mutations, all at codon 12, were found in 83 of 101 (82%) cases of PDA and 10 of 11 (91%) cases of undifferentiated carcinoma. Data on the 93 KRAS mutated cases are shown below.
|Pancreatic Ductal Adenocarcinomas (n=83)||Undifferentiated Carcinomas (n=10)|
|Female/Male||39 / 44||5 / 5|
|Most common KRAS mutations||G12D (55%), G12V (28%)||G12D (40%), G12V (40%)|
|KRAS allele peak heights on sequencing electropherograms:|
|KRAS/CEP12 by FISH:|
|>2||0 /18||5 / 9|
|<2||18 /18||4 / 9|